Current progress in metabolomics of gestational diabetes mellitus

Preterm birth is a complex syndrome and remains a substantial public health problem globally. Its common complications include periventricular leukomalacia (PVL), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC) and retinopathy of prematurity (ROP). Despite great advances in the comprehension of the pathogenesis and improvements in neonatal intensive care and associated medicine, preterm birth-related diseases remain essentially without adequate treatment and can lead to high morbidity and mortality. The therapeutic potential of mesenchymal stem/stromal cells (MSCs) appears promising as evidenced by their efficacy in preclinical models of pathologies relevant to premature infant complications. MSC-based therapeutic efficacy is closely associated with MSC secretomes and a subsequent paracrine action response to tissue injuries, which are complex and abundant in response to the local microenvironment. In the current review, we summarize the paracrine mechanisms of MSC secretomes underlying diverse preterm birth-related diseases, including PVL, BPD, NEC and ROP, are summarized, and focus is placed on MSC-conditioned media (CM) and MSC-derived extracellular vesicles (EVs) as key mediators of modulatory action, thereby providing new insights for future therapies in newborn medicine.

Obesity has become a worldwide epidemic, and obesity-related problems are becoming more severe in public health. Increasing brown adipose tissue (BAT) mass or/and activity in mice and humans has been demonstrated to help lose weight and improve whole-body metabolism. Studies on the conversion of white adipose tissue (WAT) to BAT under certain conditions have provided new possibilities for treating obesity and the related disorders. It has been established that long non-coding RNAs (lncRNAs) play an important role in the regulation of mouse adipocyte differentiation and thermogenic programs; however, the function and potential mechanism of lncRNA in the process of human white adipocyte browning remains unclear. In the present study, we identified a lncRNA called Forkhead Box C2 antisense RNA 1 (FOXC2-AS1), which was first identified in osteosarcoma, and it was highly expressed in human adipocytes but decreased during the white adipocyte differentiation program. FOXC2-AS1 expression was also induced by the thermogenic agent forskolin. Lentivirus-mediated overexpression of FOXC2-AS1 in human white adipocytes did not affect lipid drop accumulation, but significantly promoted the browning phenotype, as revealed by the increased respiratory capacity and the enhanced protein expression levels of brown adipocyte-specific markers. In contrast, inhibiting FOXC2-AS1 with small interfering RNA led to attenuated thermogenic capacity in human white adipocytes. RNA-sequencing analysis and western blot were used to identify a possible regulatory role of the autophagy signaling pathway in FOXC2-AS1 to mediate white-to-brown adipocyte conversion. The autophagy inhibitor 3-methyladenine restored the reduced UCP1 protein level and thermogenic capacity caused by inhibiting FOXC2-AS1. Overall, the present study characterized the potential role of FOXC2-AS1 and further identified a lncRNA-mediated mechanism for inducing browning of human white adipocytes and maintaining thermogenesis, further providing a potential strategy for treating obesity and related disorder.

Background: The presence of sarcopenia in patients with chronic kidney disease (CKD) is associated with poor prognosis. The mechanism underlying CKD‐induced muscle wasting has not yet been fully explored. This study investigates the influence of renal secretions on muscles using multiomics sequencing. Methods: The kidney transcriptome analysis by RNA‐seq and protein profiling by tandem mass tag (TMT), serum TMT and muscle TMT were performed in CKD established using 0.2% adenine and control mice. Spp1 recombinant protein was used to study its effect on myotube atrophy in vitro. In animal experiments on CKD, pharmacological inhibition of Spp1 was used to explore the role of Spp1 in skeletal muscle wasting. Transcriptome analysis was performed to identify differentially expressed genes (DEGs) in the gastrocnemius muscle following Spp1 pharmacological inhibition. Results: In the renal transcriptome and TMT, 503 and 377 proteins/genes respectively were co‐upregulated and co‐downregulated. In the serum TMT of CKD and normal control (NC) mice, 22 upregulated and 7 downregulated differentially expressed proteins (DEPs) showed the same expression patterns as those in the kidney transcriptome and TMT analysis. Based on bioinformatics analysis and reported studies, we selected Spp1 for further validation. Spp1 recombinant protein was added to C2C12 myotubes in vitro, and the results indicated that Spp1 significantly increased the protein levels of the muscle atrophy marker (Murf‐1) and promoted the smaller myotubes (all p < 0.05). Compared with NC mice, Spp1 mRNA and protein levels were significantly upregulated in the kidneys of CKD mice, and the serum concentration of Spp1 was also markedly increased (all p < 0.05). In animal experiments, pharmacological inhibition of Spp1 increased the weights of gastrocnemius and tibialis anterior muscles ( p < 0.05) and improved muscle atrophy phenotype. Transcriptome analysis showed that DEGs in the gastrocnemius muscle following Spp1 pharmacological inhibition were enriched in protein digestion and absorption, glucagon signalling pathway, apelin signalling pathway and ECM‐receptor interaction pathway. Conclusions: Our study is the first to establish a regulatory network of kidney‐muscle crosstalk to explore the potential mechanism of CKD‐related sarcopenia. Employing multiomics analysis, cellular assessment and animal experiments, we have identified that Spp1 could potentialy serve as a promising therapeutic target for CKD patients with sarcopenia.